Vaccines related epidemiology

Programme design and policy options

First EpiTrain course in Advanced Epidemiology Jurmala Latvia 29.10.2004

Hanna Nohynek KTL Helsinki Finland

Vaccination Policy Options

?

Eradication Activities New Vaccine Introduction Outbreak vs routine control of epidemic diseases Newer Vaccine Research and Development

1

Evolution of Immunization Programmes

2

Pre-vaccine Increasing Coverage

3

Loss of Confidence

4

Resumption of Confidence

5

Eradication Disease Vaccinations Stops Outbreak Vaccine Coverage Adverse Events Maturity of programme

Ref: Grabenstein JD, Hospital Pharmacy 1996

When planning vaccinating (an individual or) a population

Vaccine efficacy Severity of disease Risk to contract Coverage Adverse events Price

Basic questions when introducing new vaccines into a national programme

• • • • • •

Is the vaccine efficacious enough and safe ? Is there big enough vaccine preventable disease burden in the country ? Is the public aware of the importance of the disease ?

Is the vaccine coverage good ?

How could the vaccine be introduced into the national schedule ?

How can the country assure availability of the vaccine in long term ?

Decision making processes for introducing new vaccines vary greatly in industrialized countries Reasons

-

national health systems in place

-

funding basis of programme

-

gross national product

-

national prioritization health vs. other values within health

Case Finland: Rationale and aims of changes in programme 2001-

Opportunity to make major revisions arising from decision to stop national vaccine production (to end by December 2004) Best possible/affordable protection to whole population National consensus process Revisions need to base on scientific evidence and cost effectiveness evaluation Carefully controlled implementation Follow up of implementation and evaluation of effectiveness

Age National vaccination programme in 2001 Vaccine Injections

<1 weeks 3 mo 4 mo 5 mo 6 mo 12 mo BCG DTwP DTwP + Hib DTwP Polio + Hib Polio 14-18 mo MMR + Hib 20-24 mo DTwP + polio

Possible programmatic changes discussed

New combination vaccine to replace wP in DTwP Reductions / omissions BCG Add ons hepatitis B, pertussis, influenza, pneumococcus (PPV), tick born encephalitis (regionally) New vaccines varicella, pneumococcus (PCV), (meningococcus C)

Costs of the Finnish nEPI

Milj. € Vaccination programme in 2002 DTaP-Hib-IPV x 3 Savings from stopping own production and single doses 4,54 4,20 -1,68 d/DTaP to >6-year olds Influenza to >65-year olds 0,77 0,89 New (mandatory additions) 8,72 Population 5.2 mi, birth cohort 60 000

nEPI costs...

New (mandatory additions) BCG-vaccine reductions Stopping polio boosters New (minimum) Milj. € 8,72 -0,03 -0,49 8,20

Costs of new nEPI ?

Milj. € New (minimum) Varicella x 2 Pnc-conjugate x 4 Hepatitis B -vaccine x 3 (part of a combo vacc) 8,20 3,93 12,11 1,51 New (maximum) 25,75 = 5 - fold difference !

Roles and responsibilities in decision making for nEPI

Ministry of Health National Advisory Committee for Infectious Diseases National Public Health Institute (KTL) National Advisory Committee for Vaccination (KRAR) KTL Advisory Board on Vaccines Disease / Vaccine Specific working groups

Disease / vaccine specific subgroup reports

• Pertussis • BCG • Varicella • Influenza VE evidence categorized according to ~EBM Cost effectiveness analyses • Pneumococcus (PPS, PCV) • Combination vaccines • Hepatitis B • TBE

New decision making process adopted = 4 steps approach

Factors to consider 1) Expected public health benefit 2) Safety of vaccine individually 3) Safety effects on population level 4) Benefit / cost of vaccine

Outcome of the 4 step evaluation for 7PCV 1) Expected public health benefit +

Efficacy of PncCRM vaccine

3ISPPD 2002 NCKP Arizona Soweto NCKP Arizona (RSV-) Soweto (HIV-) Soweto (HIV+) FinOM (VT) FinOM (PNC) FinOM (all) NCKP (all)

Invasive Infections Pneumonia (X-ray positive) Acute Otitis

0 10 20 30 40 50 60 70 80 90 100

%

Invasive Pnc infections in Finland in 1995-99

Cases/year

100 80 60 40 20 0

67,5 % <5 5-9 10 14 15 19 20 24 7PCV serotype coverage 25 29 30 34 Incidence/100 000/year 49,4%

30 25 20 15 10 5

35 39 40 44 45 49 50 54 55 59 60 64 65 69

0

70 74 >75 Age, years Source: National Register for Infectious Diseases

Incidence of pneumonia strongly affected by case definition Also has an impact on expected VE of PCV

FinOM cohort Pilot study

Incidence of

AOM / 100 childmonth 20 18 16

Acute Otitis Media

AOM is most common among children 7-12 mo of age.

14 12

All AOM

10 8 6 4 2 0

AOM by Pnc

2 3 5 7 9 11 13 15 17 19 21 23 Age, months Kilpi et al. Pediatr Infect Dis J 2001;20:654-62

Pnc disease burden in Finland

Birth cohort 60 000 Universal use of 7PCV potentially prevents annually 50 - 60 cases of IPD 500 - 1 800 cases of pneumonia 10 000 episodes of AOM 2 400 otologic surgery procedures

4 steps approach for 7PCV

1) Expected public health benefit + 2) Safety of vaccine + large scale RC trials demonstrated safety on individual level

4

steps approach for 7PCV

1) Expected public health benefit + 2) Safety of vaccine + 3) Population level effects + herd effect ?/ replacement

4 steps approach for 7PCV

1) Expected public health benefit + 2) Safety of vaccine + 3) Population level effects + herd effect, ? replacement 4) Benefit / cost of vaccine - with 4 doses

Costs € of introducing 7PCV into national program

Cost category

Total medical Vaccination programme Health care Travel Total direct

Productivity

Total cost No 7PCV

26 486 016 0 26 486 016 1 342 152

27 827 169 Yes 7PCV

22 303 132 11 929 766 34 232 898 1 226 297

35 459 195

Net cost € - 4 182 884 11 929 766 7 746 882 - 114 856

+ 632 026

11 798 063

32 625 232

10 348 785

45 807 980

- 1 449 277

+6 182 749 Salo H et al. ESPID 2003

Cost effectiveness of 7PCV in Finland

1) The price of 7PCV should be third (half) the price 2) Effect of reducing number of 7PCV doses and/or using 23PncPS for boosting needs to be evaluated 3) Benefits = quality of life > life years saved

Salo H et al. ESPID 2003

Conclusion from step 4 evaluation

Introduction of 4 doses of 7PCV would almost triple the costs of universal childhood vaccination program compared to the 2001 level, even if all savings achieved by reduced disease burden were taken into account.

Final conclusion

Expert consensus: even if pneumococcus causes substantial public health disease burden, 7PCV is safe and possibly has positive herd effect extending to older age groups,

7PCV is not cost efficacious if given according to the recommended 4-dose schedule; therefore, at the time being 7PCV is not recommended to be implemented

into national vaccination program in Finland.

Further comment by WG

Introduction of new vaccines should not be compared to introduction of old vaccines Right comparision = new vaccines vs. any other preventive health intervention (screening for prostate cancer, hip replacement, etc.)

Further comment by WG

1. Introduction of new vaccines should not be compared to introduction of old vaccines (screening for prostate cancer, hip replacement, etc.) 2. Any health intervention to be introduced should have a firm scientific evidence base 3. Limited resources should be targeted at interventions with equal benefit obtained with least amount of costs

In October 2004, Finland is

-

Getting ready to introduce a new routine infant immunization programme without 7PCV (January 2005->)

-

Recalculating costs and benefits taking into consideration accumulating evidence of the effects of 7PCV (herd immunity, need of less than 4 doses, replacement)

Age National vaccination programme in 2004 Vaccine Injections

<1 weeks 3 mo 4 mo 5 mo 6 mo 12 mo BCG DTwP DTwP + Hib DTwP Polio + Hib Polio 14-18 mo MMR + Hib 20-24 mo DTwP + polio

Age National vaccination programme in 2005 Vaccine Injections

<1 weeks 3 mo 4 mo 5 mo 6 mo 12 mo 14-18 mo BCG DTaP-Polio-Hib DTaP-Polio-Hib DTaP-Polio-Hib MMR 20-24 mo

Hep B immunization policy WHO European Region, 2004 Universal newborn Universal infant Universal adolescent No universal Hep B Immunization 11 countries receiving support from GAVI/VF

Haemophilus influenza type b immunization WHO European Region 2004

Euro52.shp

Universal infant Part of the country Not introduced No Data Source: Joint reporting form as of 30/09/2004

Hib3 coverage in the WHO European Region 2003

>95 90-95 80-90 <80 No data No immunization

Annual incidence of Hib meningitis in children <5 years of age before the introduction of immunization based on about 70 studies in countries of the WHO European Region

50 45 40 max min 35 30 25 20 15 10 5 0

• • • •

Other new and under-used antigens in the European Region (as shown on the WHO/UNICEF Joint Reporting Forms for 2003) Accellular pertussis vaccine

(aP and aP containing vaccines) –

25 countries (WE and CCEE) Meningococcal conjugate vaccine

–

10 WE countries Pneumococcal conjugate vaccine

–

6 WE countries Varicella vaccine

–

2 WE countries

How accurate is this information?

• • •

Vaccine programmes for the rich vs. poor

Rich: DTP, IPV, MMR + HBV, Hib + Varicella, PCV + Influenza Poor: BCG, DTP, OPV, M + HBV, (Hib) -> GAVI 13 12 5 6 7 11 10 9 8 Rich Poor 1975 1985 1995 2004